Vaccine最新文献

Monkeypox virus (MPXV), a zoonotic orthopoxvirus closely related to variola virus, is a double-stranded DNA (dsDNA) virus in the Orthopoxvirus genus, which includes vaccinia and cowpox viruses. Identified in 1958 and first documented in humans in 1970, MPXV poses substantial public health challenges. Its origins remain uncertain, but African rodents like fire-footed rope squirrels and non-human primates are potential reservoirs. Recent global outbreaks have highlighted the urgent need for effective vaccination strategies to mitigate morbidity, mortality, and transmission risks. Approved vaccines such as ACAM2000 and MVA-BN demonstrate efficacy in preventing MPXV infection, with MVA-BN offering a safer profile, particularly for immunocompromised individuals. Emerging platforms, including mRNA and multivalent vaccines, show promise in enhancing immune responses and addressing limitations of traditional vaccines. Preclinical studies highlight significant advancements in rapid-deployment technologies, enabling robust humoral and cellular immunity against MPXV. Current vaccination strategies against MPXV provide foundational tools for outbreak control; however, gaps remain in accessibility, safety, and scalability. Equitable vaccine distribution and investment in research are essential to address the global mpox threat effectively.

Canine distemper virus, CDV, is a worldwide distributed disease of the genus Morbillivirus that can affect dogs of all ages, breeds, and both sexes with varying degrees of morbidity and lethality. The virus consists of six structural proteins, of which the Hemagglutinin is responsible for the efficient fusion to the cell membrane, allowing the virus entrance and replication in susceptible animals. The Hemagglutinin protein is responsible for the virus binding to the SLAM and Nectin-4 proteins present on the host cell membrane to start the infection process. This biochemical mechanism is then used to develop vaccines. However, due to the Hemagglutinin amino acid sequence being highly variable in several countries, animals that are vaccinated develop CDV symptoms. To evaluate this low vaccine efficiency in Brazil, this study explores the genetic and molecular basis to understand the differences in the Hemagglutinin phylogenetic profile compared to the vaccine strains. Specifically, Hemagglutinin, SLAM, and Nectin-4 interaction regions are compared to find amino acid mutations responsible for this behavior. For this purpose, a set of molecular modelling programs and protocols was used. Phylogenetic analysis of 102 Hemagglutinin genes highlighted the distances between several groups from the vaccine and the Brazilian strains. To understand the virus recognition specificities, a set of eighteen new tridimensional structures of this receptor was proposed - eleven Brazilian and seven vaccine strains. Despite the high structural similarities, the conformational comparison shows important differences in amino acids on the Hemagglutinin interaction site with SLAM and Nectin-4. Clearly, this lack of the strains circulating in Brazil and the commercial vaccine may explain the protocol failures due to the absence of specific antibodies in the animals to recognize most local CVD, thus evidencing the need for biotechnological efforts to produce vaccines considering a wider range of strains.

To better inform pneumococcal immunization policies, ongoing surveillance for pneumococcal community-acquired pneumonia (CAP) is crucial. To estimate the serotype-specific CAP burden of pneumococcal disease following the introduction of a new 15-valent pneumococcal conjugate vaccine (PCV), V114, a 15-plex serotype-specific urine antigen detection (SSUAD) assay was developed as a tool for surveillance of Streptococcuspneumoniae serotypes. V114-017 (NCT03547167; EudraCT 2017-004915-38) was a phase 3 randomized controlled trial in which participants (18-49 years) received V114 or 13-valent PCV (PCV13; as an active comparator), followed 6 months later by 23-valent pneumococcal polysaccharide vaccine (PPSV23). Here, we report findings from a prespecified sub-study nested within the phase 3 trial that descriptively assessed the impact of nasopharyngeal/oropharyngeal (NP/OP) carriage and pneumococcal vaccination on serotype detection with the SSUAD assay. In total, 301 individuals (all American Indian/Alaska Native) participated in the sub-study. NP/OP and urine samples were collected at 10 timepoints between baseline (prior to vaccination) and Month 7 (30 days following vaccination with PPSV23). NP/OP carriage was determined using qualitative polymerase chain reaction for pneumococcus detection and serotyping, and urine samples were tested in parallel with SSUAD. At any timepoint, NP/OP carriage was <2.0 % for 10 of the V114 serotypes; carriage was ∼2.6 % for serotype 1 and ranged between 4.0 % and 7.0 % for serotypes 4, 5, 9V, and 33F. At baseline, serotype-specific pneumococcal polysaccharide antigens were detected by SSUAD in only six study participants for serotypes 19A, 19F, and 1. SSUAD positivity for serotypes 4, 5, and 9V increased transiently following vaccination with V114/PCV13 and PPSV23, while SSUAD positivity lasted the longest for serotype 19A following PPSV23 vaccination. In general, SSUAD positivity appeared unrelated to NP/OP carriage. Our findings suggest SSUAD can support pneumococcal disease surveillance and vaccine effectiveness research, excluding individuals with recent pneumococcal vaccination to avoid false-positives.

Continuous boosting with the original vaccines based on the Ancestral (Wuhan hu-1) strain to maintain immunity has not been sufficient to detain the emergence and rapid dissemination of viral variants. This study was to evaluate the immune responses and safety of a heterologous boost with bivalent Original/Omicron BA.4-5 vaccine mRNA vaccine given after at least 12 months to those who had been primed with NDV-HXP-S COVID -19 vaccine (an inactivated recombinant Newcastle disease virus vaccine).

Methods: An open-label study assessing the booster effects of the bivalent mRNA vaccine given to those who were primed with two doses of the NDV-HXP-S COVID-19 vaccine (either 3 μg with or without the CpG1018 adjuvant or 10 μg of NDV-HXP-S) at least one year ago. The immune responses were measured accordingly.

Findings: The bivalent mRNA boost was safe. Corresponding geometric mean fold rise (GMFRs) in NT₅₀ against Ancestral strain at D28 were 4.4, 3.3, and 3.6 and further increased to 7.8, 6.6 and 6.3 by D90 in the 3 μg, 3 μg + CpG and 10 μg dose groups, respectively. In contrast, the GMFR NT50 against XBB.1.5 peaked at D28 to 11.8, 11.3 and 8.4 and declined to 3.3, 4.0 and 2.6 at D90 in the three dose groups, respectively. Regarding the IFN-gamma response, the group primed with 3 μg + CpG had a greater T cell response by D90 than the other two groups. There was a trend in higher NT₅₀ against XBB.1.5 after boosting, especially among participants in the hybrid-immune subgroup who had a SARS-CoV-2 infection more than 12 months. No safety concerns reported.

Conclusion: The immune responses stimulated by the heterologous boost with bivalent mRNA vaccine in the NDV-HXP-S primed groups were high especially among the hybrid immune subgroup. Thai Clinical Trial Registry: WHO REGISTRY PLATFORM- TCTR20230809003.

Introduction: Despite the success of vaccination, isolated cases of COVID-19 infection are being reported in the vulnerable subjects worldwide. Given that individuals with type-2 diabetes (T2D) often exhibit immune dysregulation, this study aimed to characterize SARS-CoV-2-specific immunity following ChAdOx1 nCoV-19 vaccination in subjects with T2D.

Methods: We recruited 55 T2D and 60 healthy control (HC) subjects and monitored their immunological parameters at baseline, 3rd, 6th, and 12th month post-ChAdOx1 nCoV-19 vaccination. The frequency of SARS-CoV-2 epitope-specific CD8+ T cells were determined using MHC-I dextramers. The SARS-CoV-2 specific recall responses were assessed by lymphocyte proliferation, intracellular (TNF-α, IFN-γ) and extracellular (IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β) cytokine estimation following in-vitro stimulation with SARS-CoV-2 S-protein peptide pool (SP). The anti-S antibody titers and the frequency of memory B cells (CD19+ CD27+), plasmablasts (CD19+ CD27hiCD38hi), and plasma cells (CD38hi CD138+) were also determined.

Results: Following vaccination, the incidence of COVID-19 disease was significantly higher in T2D individuals, suggesting an increased rate of breakthrough infections. The T2D cohort also exhibited lower frequency of SARS-CoV-2-specific peripheral CD8+ T cells and demonstrated diminished recall responses, as evidenced by reduced in-vitro lymphocyte proliferation. During breakthrough COVID-19 disease, systemic levels of IFN-γ were elevated in T2D subjects, whereas higher IL-10 levels were observed only in HC. Upon SP stimulation, a greater proportion of CD8+ and CD4+ T cells from HC expressed IFN-γ and TNF-α, indicating a more robust antiviral cell-mediated immune response. Additionally, B cell immunophenotyping revealed a reduced frequency of memory B cells in T2D.

Conclusion: The data indicate that individuals with T2D exhibit impaired vaccine-induced SARS-CoV-2-specific immunological memory, in contrast to HC, who demonstrate a well-regulated balance between pro- and anti-inflammatory responses.

Despite evidence that maternal vaccines can contribute to reduction of neonatal infections, vaccine hesitancy is a challenge in many low- and middle-income countries like Uganda. We conducted in-depth interviews with pregnant women and focus group discussions with breastfeeding women who were part of a Group B Streptococcus (GBS) clinical trial. We explored the women's concerns about vaccination and their reasons for being hesitant to take vaccines before they joined the trial. Women aged 18-39 were randomly selected from follow-up lists during the study period. Data were analysed thematically. All the women had been hesitant about joining the trial because of fear of possible vaccine side effects. A lack of knowledge on maternal vaccines, rumours and stigma in the community as well the need to follow study procedures were other concerns. Several women were concerned about their male partner view of their trial participation because using a trial vaccine meant taking a decision on behalf of the foetus. Pregnant women's involvement in clinical trials of maternal immunisation requires engagement with their families and community stakeholders, including local leaders and health workers, to ensure people understand what maternal vaccines are and why trials with pregnant women are required.

Background: There is limited data regarding SARS-CoV-2 vaccine uptake in people with HIV (PWH) compared to people without HIV (PWoH).

Methods: Swedish nationwide study of individuals born 1930-2003, assessing SARS-CoV-2 vaccine uptake of 1-5 doses by HIV-status from first SARS-CoV-2 vaccination (2020-12-27) until 2023-02-23. PWH were categorized by prioritization: clinically vulnerable (CD4+ T-cells <50cells/μL, recent opportunistic disease, or CD4+ T-cells <200 in combination with detectable HIV-RNA > 200copies/mL), and not prioritized (non-vulnerable PWH). Relative risks (adjRR) for doses 1-5 were estimated using modified Poisson regression, adjusted for sociodemographics, SARS-CoV-2 infections, and comorbidities.

Results: 7233 non-vulnerable PWH, 435 clinically vulnerable PWH, and 8,168,340 PWoH were included. While unadjusted 3-dose uptake was lower in both PWH groups compared to PWoH, adjusted analysis showed higher uptake in non-vulnerable PWH (adjRR1.17, 95 % CI 1.15-1.19), with similar trends in clinically vulnerable. An interaction between country of birth and HIV-status was identified (p < 0.001). Migrants with HIV had higher 3-dose uptake vs. migrants without HIV, but were less likely vaccinated than Swedish-born with HIV. Among people ≥65 years old, PWH were less likely to receive 3 or more doses compared to PWoH ≥65 years (dose 5: adjRR 0.90, 95 % CI 0.85-0.96).

Conclusions: We found lower vaccination uptake in migrants, irrespective of HIV-status, consistent with previous studies. Most concerningly we identified a lower vaccine uptake among people with HIV who were 65 years or older. This nationwide study highlights the need for targeted vaccination strategies and interventions that address both HIV-status and demographic factors.

Introduction: Vaccine misinformation has been increasingly pervasive since the COVID-19 pandemic. It was a particular challenge among Arabic-speaking communities during vaccine roll-out. This study explored the content, context and mechanisms of vaccine misinformation beliefs and dissemination among the Arabic-speaking community in Victoria, to inform the adaptation of the Cranky Uncle - Vaccine (Arabic) online misinformation inoculation game.

Methods: This qualitative study involved exploratory community focus groups and intervention adaptation workshops. Using convenience sampling, the project's Advisory Group disseminated flyers to Arabic-speaking communities through their networks, in-person and online. Semi-structured discussions used the transcendental (descriptive) phenomenological approach to explore the 'who, 'what', 'where', 'when' of vaccine misinformation dissemination to inform intervention adaptation and utility. Data were combined and inductively thematically analysed.

Results: Four online focus group discussions were held with 16 women (16-70+ years) in total. Sixty-five participants (n = 45 female, 16-70+ years) attended one of two face-to-face workshops. Arabic translators assisted in three focus groups and both workshops. Misinformation about COVID-19 vaccines (but not other vaccines) was easily recalled, and the content aligned with misinformation topics identified elsewhere, e.g. vaccine concerns and conspiracy theories. Regarding context, the information context theme reflected an information gap that encouraged individuals to seek out vaccine information via unofficial sources. The personal context theme was of fear and uncertainty of the vaccine's side effects, and secondarily of mistrust in authorities. In terms of dissemination mechanisms, misinformation was shared through friends and family and was image-based, making it accessible regardless of written or social media literacy. Misinformation was believed when it filled information gaps, was emotive and reinforced fears and beliefs.

Discussion: The findings support the utility of the Cranky Uncle - Vaccine (Arabic) game in inoculating key audiences. The community-centred approach to game adaptation makes it relatable and directly relevant to audiences' vaccine beliefs and concerns.

Background: People infected with human immunodeficiency virus (HIV) are more likely to be infected with hepatitis B virus (HBV), which is a significant public health concern. It is essential to provide protection through the hepatitis B vaccine and to stimulate higher and more sustained levels of anti-HBs antibodies to ensure long-term immunity. We aimed to enhance the duration of immunogenicity by implementing high-dose and multiple-schedule hepatitis B vaccination in adults infected with HIV.

Methods: This open-label, parallel-group, randomised controlled trial (RCT) was conducted between May 2020 and January 2021 at the Second Hospital of Yuncheng. Patients were randomised to receive 3 or 4 doses of 20 μg or 60 μg of hepatitis B vaccine. The follow-up period was extended to 2022 to evaluate the duration of immunogenicity.

Results: The geometric mean concentration (GMC) and response rates of hepatitis B surface antibody (anti-HBs) at month 18 were 200.40 mIU/ml and 66.67 % (58/87) in the IM20 × 3 group, 382.20 mIU/ml and 75.58 % (65/86) in the IM20 × 4 group, 628.50 mIU/ml and 83.13 % (69/83) in the IM60 × 4 group, which were significantly different between the IM20 × 3 and IM60 × 4 groups (P < 0.017). In multivariate analysis, gender and vaccination regimens affected the duration of immunogenicity at month 18. Regarding the multiplicative scale, the interaction effect was significant between the male and the IM60 × 4 group after adjusting for confounders.

Conclusion: In the one-year follow-up (month 18) of adults infected with HIV, four triple doses regimen of hepatitis B vaccine improved the duration of immunogenicity in male patients.